Derivatives of 5-Aryl-1H-Pyrrolo [2, 3B] Pyridine-3-Carboxamide or 5-Aryl-1H-Pyrrolo [2, 3B] Pyridine-3-Carboxylic Acid

Abstract

The present invention relates to new compounds of formula I as a free base or a pharmaceutically acceptable salt, solvate or solvate of salt thereof, a process for their preparation and new intermediates used therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds in therapy.

1 . A compound of the formula I: 
     
       
         
         
             
             
         
       
       wherein: 
       P is phenyl or a 5- or 6-membered heteroaromatic ring containing one or more heteroatoms selected from N, O or S and said phenyl or 5- or 6-membered heteroaromatic ring may optionally be fused with a 5- or 6-membered saturated, partially saturated or unsaturated ring containing one or more atoms selected from C, N, O or S; 
       Q is independently selected from C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, or Q is absent; 
       X is independently selected from N or O and when X is O, Q and R 4  are absent; 
       R is independently selected from hydrogen, CN, NO 2 , OH, NH 2 , COOH, CONH 2 , COCH 3 , halogen, C 1-6 alkyl, C 1-6 alkoxy, fluoromethyl, difluoromethyl, trifluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy; 
       R 1  is independently selected from C 1-6 alkylC 3-6 cycloalkyl, OR 5 , SR 5 , NR 6 R 7 , CO 2 R 5 , COR 5 , (SO 2 )R 5 , (SO)R 5 , (SO 2 )NR 6 R 7 , NR 8 (SO 2 )R 5 , CONR 6 R 7 , NR 8 COR 5 , NR 8 CONR 6 R 7 , NR 8 CO 2 R 5 , (SO)NR 6 R 7 , NR 8 (SO)R 5 , C 1-6 alkylOR 5 , C 1-6 alkylSR 5 , C 1-6 alkylNR 6 R 7 , C 1-6 alkylCO 2 R 5 , C 1-6 alkylCOR 5 , C 1-6 alkyl(SO 2 )R 5 , C 1-6 alkyl(SO)R 5 , C 1-6 alkyl(SO 2 )NR 6 R 7 , C 1-6 alkylNR 8 (SO 2 )R 5 , C 1-6 alkylCONR 6 R 7 , C 1-6 alkylNR 8 COR 5 , C 1-6 alkylNR 8 CONR 6 R 7 , C 1-6 alkylNR 8 CO 2 R 5 , C 1-6 alkyl(SO)NR 6 R 7  or C 1-6 alkylNR 8 (SO)R 5 ; and wherein said C 1-6 alkyl group is optionally substituted by one or more A; 
       R 2  is independently selected from hydrogen, C 1-6 alkyl, CN, nitro, halogen, OR 13 , fluoromethyl, difluoromethyl, trifluoromethyl, fluoromethoxy, difluoromethoxy and trifluoromethoxy; 
       R 3  is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 0-6 alkylC 3-6 cycloalkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 0-6 alkylC 3-6 cycloalkyl group is optionally substituted by one or more A; 
       R 4  is independently selected from hydrogen, halogen, nitro, CHO, CN, OC 1-6 alkylCN, OR 13 , OC 1-6 alkylOR 13 , fluoromethyl, difluoromethyl, trifluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, NR 13 R 14 , OC 1-6 alkylNR 13 R 14 , NR 13 OR 14 , CO 2 R 13 , OC 1-6 alkylCO 2 R 13 , CONR 13 R 14 , OC 1-6 alkylCONR 13 R 14 , OC 1-6 alkylNR 13 (CO)R 14 , NR 13 (CO)R 14 , O(CO)NR 13 R 14 , NR 13 (CO)OR 14 , NR 13 (CO)NR 13 R 14 , O(CO)OR 13 O(CO)R 13 , COR 13 , OC 1-6 alkylCOR 13 NR 13 (CO)(CO)R 14 , NR 13 (CO)(CO)NR 13 R 14 , SR 13 , (SO 2 )NR 14 R 13 , OC 1-6 alkylNR 13 (SO 2 )R 14 , NR 5 (SO 2 )R 13 , OC 0-6 alkyl(SO 2 )NR 13 R 14 , (SO)NR 13 R 14 , OC 1-6 alkyl(SO)NR 13 R 14 , SO 3 R 13 , NR 5 (SO 2 )NR 13 R 14 , NR 13 (SO)R 14 , OC 1-6 alkylNR 13 (SO)R 14 , OC 0-6 alkylSO 2 R 13 , SO 2 R 13 , SOR 13 , C 3-6 cycloalkyl, aryl, a 5- or 6-membered heteroaromatic ring containing one or more heteroatoms independently selected from N, O, or S, a 5- or 6-membered heterocyclic ring containing one or more heteroatoms independently selected from N, O, or S, which heterocyclic group may be saturated or unsaturated, or R 4  may be absent, and wherein any said C 3-6 cycloalkyl, aryl, 5- or 6-membered heteroaromatic ring or a 5- or 6-membered heterocyclic ring is optionally substituted by one or more A, or R 4  may be absent; 
       R 5  is independently selected from C 3-6 cycloalkyl, C 1-6 alkylC 3-6 cycloalkyl, C 2-6 alkylNR 9 R 10 , C 2-6 alkylOC 2-6 alkylNR 9 R 10 , C 2-6 alkyl(SO 2 )NR 9 R 10 , C 2-6 alkyl(SO)NR 9 R 10 , C 2-6 alkylNR 11 (SO)R 12 , C 2-6 alkylNR 9 (SO 2 )R 10 , C 2-6 alkyl(SO 2 )C 2-6 alkylNR 9 R 10 , C 2-6 alkyl(SO)C 2-6 alkylNR 9 R 10 , C 2-6 alkylSC 2-6 alkylNR 11 R 12 , C 2-6 alkylCONR 9 R 10 , C 2-6 alkylNR 9 COR 10 , heteroaryl or C 1-6 alkylheteroaryl wherein any C 2-6 alkyl or heteroaryl is optionally substituted by one or more A; 
       R 6  is independently selected from C 2-6 alkenyl, C 2-6 alkynyl, C 0-6 alkylC 3-6 cycloalkyl, C 1-6 alkylNR 9 R 10 , C 1-6 alkylOC 1-6 alkylNR 9 R 10 , C 0-6 alkyl(SO 2 )NR 9 R 10 , C 1-6 alkyl(SO)NR 9 R 10 , C 1-6 alkylNR 11 (SO)R 12 , C 1-6 alkylNR 9 (SO 2 )R 10 , C 0-6 alkyl(SO 2 )C 1-6 alkylNR 9 R 10 , C 1-6 alkyl(SO)C 1-6 alkylNR 9 R 10 , C 2-6 alkylSC 2-6 alkylNR 11 R 12 , C 1-6 alkylCONR 9 R 10 , C 0-6 alkylNR 9 COR 10 , C 1-6 alkylaryl or C 0-6 alkylheteroaryl wherein any C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 0-6 alkylC 3-6 cycloalkyl, C 1-6 alkylaryl, C 0-6 alkylheteroaryl is optionally substituted by one or more A; 
       R 7  is independently selected from hydrogen and C 1-6 alkyl; 
       R 6  and R 7  may together form a 5- or 6-membered heterocyclic ring containing one or more heteroatoms selected from N, O or S, wherein said heterocyclic ring is optionally substituted by one or more A; 
       R 8  is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 0-6 alkylC 3-6 cycloalkyl; 
       R 9  is independently selected from C 1-6 alkyl-B, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 1-6 alkylC 3-6 cycloalkyl, aryl, C 1-6 alkylaryl, heteroaryl, C 1-6 alkylheteroaryl wherein any C 3-6 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkylC 3-6 cycloalkyl, aryl, C 1-6 alkylaryl, heteroaryl, C 1-6 alkylheteroaryl is optionally substituted by one or more A; 
       R 10  is independently selected from hydrogen and C 1-6 alkyl; 
       R 9  and R 10  may together form a 5- or 6-membered heterocyclic ring containing one or more heteroatoms selected from N, O or S, wherein said heterocyclic ring is optionally substituted by one or more A; 
       R 11  and R 12  are independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 1-6 alkylC 3-6 cycloalkyl, aryl, C 1-6 alkylaryl, heteroaryl, C 1-6 alkylheteroaryl, wherein any C 3-6 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkylC 3-6 cycloalkyl, aryl, C 1-6 alkylaryl, heteroaryl, C 1-6 alkylheteroaryl is optionally substituted by one or more A; 
       R 11  and R 12  may together form a 5- or 6-membered heterocyclic ring containing one or more heteroatoms selected from N, O or S, wherein said heterocyclic ring is optionally substituted by one or more A; 
       R 13  and R 14  are independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 1-6 alkylC 3-6 cycloalkyl, C 1-6 alkylNR 15 R 16 , aryl, C 1-6 alkylaryl, heteroaryl, C 1-6 alkylheteroaryl, wherein any said C 3-6 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkylC 3-6 cycloalkyl, aryl, C 1-6 alkylaryl, heteroaryl, C 1-6 alkylheteroaryl is optionally substituted by one or more A; 
       R 13  and R 14  may together form a 5- or 6-membered heterocyclic ring containing one or more heteroatoms selected from N, O or S, wherein said heterocyclic ring is optionally substituted by one or more A; 
       R 15  and R 16  are independently selected from hydrogen and C 1-6 alkyl; 
       R 15  and R 16  may together form a 5- or 6-membered heterocyclic ring containing one or more heteroatoms selected from N, O or S, wherein the said heterocyclic ring is optionally substituted by one or more A; 
       m is 1; 
       n is 1 or 2; 
       A is selected from: halogen, nitro, oxo (═O), CHO, CN, OR 15 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 0-6 alkylC 3-6 cycloalkyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, C 0-6 alkylNR 15 R 16 , OC 1-6 alkylNR 15 R 16 , CO 2 R 15 , CONR 15 R 16 , NR 15 (CO)R 16 , O(CO)R 15 , COR 15 , SR 15 , (SO 2 )NR 15 R 16 , (SO)NR 15 R 16 , SO 3 R 15 , SO 2 R 15  or SOR 15 ; 
       B is nitro, oxo (═O), CHO, CN, OR 15 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 0-6 alkylC 3-6 cycloalkyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, C 0-6 alkylNR 15 R 16 , OC 1-6 alkylNR 15 R 16 , CO 2 R 15 , CONR 15 R 16 , NR 15 (CO)R 16 , O(CO)R 15 , COR 15 , SR 15 , (SO 2 )NR 15 R 16 , (SO)NR 15 R 16 , SO 3 R 15 , SO 2 R 15  or SOR 15 ; 
       as a free base or a pharmaceutically acceptable salt, solvate or solvate of a salt thereof. 
     
   
   
       2 . A compound according to  claim 1 , wherein P is phenyl. 
   
   
       3 . A compound according to  claim 1 , wherein R is selected from hydrogen, halogen, C 1-6 alkyl, trifluoromethyl and trifluoromethoxy. 
   
   
       4 . A compound according to  claim 3 , wherein R is selected from hydrogen and trifluoromethoxy. 
   
   
       5 . A compound according to  claim 1 , wherein R 1  is selected from NR 6 R 7 , C 1-6 alkylNR 6 R 7 , CONR 6 R 7 , (SO 2 )NR 6 R 7  and OR 5 . 
   
   
       6 . A compound according to  claim 1 , wherein R 2  is hydrogen. 
   
   
       7 . A compound according to  claim 1 , wherein R 3  is hydrogen or C 1-6 alkyl. 
   
   
       8 . A compound according to  claim 7 , wherein R 3  is hydrogen. 
   
   
       9 . A compound according to  claim 1 , wherein R 4  is independently selected from OR 13 , NR 13 R 14 , CN, SOR 13 , SO 2 R 13 , and a 5- or 6-membered heteroaromatic ring containing one or more heteroatoms independently selected from N, O, or S, or a 5- or 6-membered heterocyclic ring containing one or more heteroatoms independently selected from N, O, or S which heterocyclic group may be saturated or unsaturated, and wherein said 5- or 6-membered heteroaromatic ring or said 5- or 6-membered heterocyclic ring is optionally substituted by one or more A. 
   
   
       10 . A compound according to  claim 1 , wherein R 13  and R 14  together form a 5- or 6-membered heterocyclic ring containing one or more heteroatoms selected from N, O or S, wherein said heterocyclic ring is optionally substituted by one or more A. 
   
   
       11 . A compound according to  claim 9  or  10 , wherein said A is selected from C 1-6 alkyl, OR 15  and SO 2 R 15 . 
   
   
       12 . A compound according to  claim 1 , wherein Q is C 1-6 alkyl, or Q is absent. 
   
   
       13 . A compound according to  claim 1 , wherein X is N. 
   
   
       14 . A compound according to  claim 1  wherein R is selected from hydrogen, and trifluoromethoxy; R 1  is selected from NR 6 R 7 , C 1-6 alkylNR 6 R 7 , CONR 6 R 7 , (SO 2 )NR 6 R 7 , and OR 5 ; R 2  and R 3  is hydrogen; R 4  is independently selected from OR 13 , NR 13 R 14 , SO 2 R 13 , and a 5- or 6-membered heteroaromatic ring containing one or more heteroatoms independently selected from N, O, or S, a 5- or 6-membered heterocyclic ring containing one or more heteroatoms independently selected from N, O, or S which heterocyclic group may be saturated or unsaturated, and wherein said 5- or 6-membered heteroaromatic ring or said 5- or 6-membered heterocyclic ring is optionally substituted by one or more A; R 13  and R 14  are independently selected from hydrogen, and C 1-6 alkyl; R 13  and R 14  together form a 5- or 6-membered heterocyclic ring containing one or more heteroatoms selected from N, O or S, wherein the said heterocyclic ring is optionally substituted by a group selected from A; R 15  is C 1-6 alkyl; Q is C 1-6 alkyl, or Q is absent; A is C 1-6 alkyl, SO 3 R 15 , or OR 15 . 
   
   
       15 . A compound selected from: 
     N-(3-Methoxypropyl)-5-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     5-{4-[(4-Methylpiperazin-1-yl)sulfonyl]phenyl}-N-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-(2-Methoxyethyl)-5-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-(2-Methoxyethyl)-5-[4-[(4-methylpiperazin-1-yl)sulfonyl]-3-(trifluoromethoxy)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-(3-Methoxypropyl)-5-[4-[(4-methylpiperazin-1-yl)sulfonyl]-3-(trifluoromethoxy)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     5-[4-[(4-Methylpiperazin-1-yl)sulfonyl]-3-(trifluoromethoxy)phenyl]-N-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     5-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-N-[2-(methylsulfonyl)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-(2-Methoxyethyl)-5-[4-(morpholin-4-ylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-(3-Methoxypropyl)-5-[4-(piperidin-1-ylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     5-{4-[(4-Methylpiperazin-1-yl)methyl]phenyl}-N-[2-(methylsulfonyl)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     5-{4-[2-(4-Methylpiperazin-1-yl)ethoxy]phenyl}-N-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-(3-methoxypropyl)-5-[4-(2-morpholin-4-ylethoxy)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-(3-Methoxypropyl)-5-{4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-(3-Methoxyphenyl)-5-[4-(2-morpholin-4-ylethoxy)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-(2-Methoxyphenyl)-5-[4-(2-morpholin-4-ylethoxy)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; and 
     5-{4-[2-(4-Methylpiperazin-1-yl)ethoxy]phenyl}-N-(2-morpholin-4-ylethyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     5-[4-(2-Morpholin-4-ylethoxy)phenyl]-N-pyridin-3-yl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-[2-(Methylsulfonyl)ethyl]-5-[4-(piperidin-1-ylsulfonyl)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     5-[4-(Morpholin-4-ylmethyl)phenyl]-N-[2-(2-thienyl)ethyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-Methyl-5-[4-[(4-methylpiperazin-1-yl)sulfonyl]-3-(trifluoromethoxy)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-Methyl-5-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-Methyl-5-[4-(piperidin-1-ylsulfonyl)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-(2-Morpholin-4-ylethyl)-5-(4-morpholin-4-ylphenyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     N-(2-Morpholin-4-ylethyl)-5-[4-(pyrrolidin-1-ylcarbonyl)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; 
     5-[4-(Morpholin-4-ylcarbonyl)phenyl]-N-(2-morpholin-4-ylethyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride; or 
     5-[4-(Morpholin-4-ylmethyl)phenyl]-N-pentyl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide hydrochloride. 
   
   
       16 . A compound selected from: 
     Methyl 5-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylate; 
     Methyl 5-[4-[(4-methylpiperazin-1-yl)sulfonyl]-3-(trifluoromethoxy)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxylate; 
     Methyl 5-[4-(morpholin-4-ylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxylate; 
     Methyl 5-{4-[(4-methylpiperazin-1-yl)methyl]phenyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylate; 
     Methyl 5-[4-(piperidin-1-ylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxylate; 
     Methyl 5-[4-(2-morpholin-4-ylethoxy)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxylate; 
     Methyl 5-{4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylate; or 
     Methyl 5-[4-(piperidin-1-ylsulfonyl)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-carboxylate. 
   
   
       17 . A pharmaceutical formulation comprising as an active ingredient a therapeutically effective amount of a compound according to  claim 1  in association with a pharmaceutically acceptable excipient, carrier or diluent. 
   
   
       18 - 25 . (canceled) 
   
   
       26 . A method of prevention and/or treatment of conditions associated with glycogen synthase kinase-3, comprising administering to a mammal, including man in need of such prevention and/or treatment, a therapeutically effective amount of a compound of formula I as defined in  claim 1 . 
   
   
       27 . A method of prevention and/or treatment of dementia, Alzheimer's Disease, Parkinson's Disease, Frontotemporal dementia Parkinson's Type, Parkinson dementia complex of Guam, HIV dementia, diseases with associated neurofibrillar tangle pathologies and dementia pugilistica, comprising administering to a mammal, including man in need of such prevention and/or treatment, a therapeutically effective amount of a compound of formula I as defined in  claim 1 . 
   
   
       28 . A method according to  claim 27 , wherein the disease is Alzheimer's Disease. 
   
   
       29 . A method of prevention and/or treatment of amyotrophic lateral sclerosis, corticobasal degeneration, Down syndrome, Huntington's Disease, postencephalitic parkinsonism, progressive supranuclear palsy, Pick's Disease, Niemann-Pick's Disease, stroke, head trauma and other chronic neurodegenerative diseases, Bipolar Disease, affective disorders, depression, schizophrenia, cognitive disorders, hair loss and contraceptive medication, comprising administering to a mammal, including man in need of such prevention and/or treatment, a therapeutically effective amount of a compound of formula I as defined in  claim 1 . 
   
   
       30 . A method of prevention and/or treatment of predemented states, Mild Cognitive Impairment, Age-Associated Memory Impairment, Age-Related Cognitive Decline, Cognitive Impairment No Dementia, mild cognitive decline, mild neurocognitive decline, Late-Life Forgetfulness, memory impairment and cognitive impairment, vascular dementia, dementia with Lewy bodies, Frontotemporal dementia and androgenetic alopecia and Type I and Type II diabetes, diabetic neuropathy and diabetes related disorders, comprising administering to a mammal, including man in need of such prevention and/or treatment, a therapeutically effective amount of a compound of formula I as defined in  claim 1 . 
   
   
       31 . A method of prevention and/or treatment of bone-related disorders, comprising administering to a mammal, including man in need of such prevention and/or treatment, a therapeutically effective amount of a compound of formula I as defined in  claim 1 . 
   
   
       32 . A process for preparing a compound of formula I, wherein X, P, Q, R, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  R 16 , A, m and n are, unless specified otherwise, defined as in formula I, comprising: 
     
       
         
         
             
             
         
       
     
     amidation of a compound of formula V, to obtain a compound of formula I, by treating a compound of formula V with an amine, HN(R 3 )QR 4  preformed neat or by using a suitable solvent, optionally with the addition of a base or an acid. 
   
   
       33 . A process for preparing a compound of formula I, wherein X, P, Q, R, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  R 16 , A, m and n are, unless specified otherwise, defined as in formula I, comprising: 
     
       
         
         
             
             
         
       
     
     de-halogen coupling of a compound of formula VIII with an appropriate aryl species in a suitable solvent to give a compound of formula I.